TY - JOUR
T1 - Brief hypoxia in late gestation sheep causes prolonged disruption of fetal electrographic, breathing behaviours and can result in early labour
AU - Baburamani, Ana
AU - Tran, Nhi
AU - Castillo-Melendez, Margie
AU - Yawno, Tamara
AU - Walker, David
N1 - Funding Information:
This study was supported by grants from the National Health & Medical Research Council of Australia (NHMRC – Grant Number ID: 545925 to DWW, MCM; 436649 & 1020732 Fellowships to DWW) and Cerebral Palsy Alliance, Australia. The authors also gratefully acknowledge support from the Victorian Government's Operational Infrastructure Support Program to the Hudson Institute of Medical Research.
Funding Information:
This study was supported by grants from the National Health & Medical Research Council of Australia (NHMRC???Grant Number ID: 545925 to DWW, MCM; 436649 & 1020732 Fellowships to DWW) and Cerebral Palsy Alliance, Australia. The authors also gratefully acknowledge support from the Victorian Government's Operational Infrastructure Support Program to the Hudson Institute of Medical Research. The authors thank Mr Alex Satragno for his help with fetal surgeries; Liliana Jackanic, Jade Kearsley and the staff in the Department of Physiology (Monash University) animal house for assistance with post-surgical care of the animals; and Mrs Jan Loose and Mrs Maria Papaioannou for their technical expertise with cortisol radioimmunoassays.
Publisher Copyright:
© 2021 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/15
Y1 - 2021/6/15
N2 - Key points: Brief episodes of severe fetal hypoxia can arise in late gestation as a result of interruption of normal umbilical blood flow Systemic parameters and blood chemistry indicate complete recovery within 1–2 hours, although the long-term effects on fetal brain functions are unknown Fetal sheep were subjected to umbilical cord occlusion (UCO) for 10 min at 131 days of gestation, and then monitored intensively until onset of labour or delivery (<145 days of gestation) Normal patterns of fetal behaviour, including breathing movements, episodes of high and low voltage electorcortical activity, eye movements and postural (neck) muscle activity, were disrupted for 3–10 days after the UCO Preterm labour and delivery occurred in a significant number of the pregnancies after UCO compared to the control (sham-UCO) cohort. Abstract: Complications arising from antepartum events such as impaired umbilical blood flow can cause significant fetal hypoxia. These complications can be unpredictable, as well as difficult to detect, and thus we lack a detailed understanding of the (patho)physiological changes that occur between the antenatal in utero event and birth. In the present study, we assessed the consequences of brief (∼10 min) umbilical cord occlusion (UCO) in fetal sheep at ∼0.88 gestation on fetal plasma cortisol concentrations and fetal behaviour [electrocortical (EcoG), electo-oculargram (EOG), nuchal muscle electromyography (EMG) and breathing activities] in the days following UCO. UCO caused a rapid onset of fetal hypoxaemia, hypercapnia, and acidosis; however, by 6 h, all blood parameters and cardiovascular status were normalized and not different from the control (Sham-UCO) cohort. Subsequently, the incidence of fetal breathing movements decreased compared to the control group, and abnormal behavioural patterns developed over the days following UCO and leading up to the onset of labour, which included increased high voltage and sub-low voltage ECoG and EOG activities, as well as decreased nuchal EMG activity. Fetuses subjected to UCO went into labour 7.9 ± 3.6 days post-UCO (139.5 ± 3.2 days of gestation) compared to the control group fetuses at 13.6 ± 3.3 days post-sham UCO (144 ± 2.2 days of gestation; P < 0.05), despite comparable increases in fetal plasma cortisol and a similar body weight at birth. Thus, a single transient episode of complete UCO late in gestation in fetal sheep can result in prolonged effects on fetal brain activity and premature labour, suggesting persisting effects on fetal cerebral metabolism.
AB - Key points: Brief episodes of severe fetal hypoxia can arise in late gestation as a result of interruption of normal umbilical blood flow Systemic parameters and blood chemistry indicate complete recovery within 1–2 hours, although the long-term effects on fetal brain functions are unknown Fetal sheep were subjected to umbilical cord occlusion (UCO) for 10 min at 131 days of gestation, and then monitored intensively until onset of labour or delivery (<145 days of gestation) Normal patterns of fetal behaviour, including breathing movements, episodes of high and low voltage electorcortical activity, eye movements and postural (neck) muscle activity, were disrupted for 3–10 days after the UCO Preterm labour and delivery occurred in a significant number of the pregnancies after UCO compared to the control (sham-UCO) cohort. Abstract: Complications arising from antepartum events such as impaired umbilical blood flow can cause significant fetal hypoxia. These complications can be unpredictable, as well as difficult to detect, and thus we lack a detailed understanding of the (patho)physiological changes that occur between the antenatal in utero event and birth. In the present study, we assessed the consequences of brief (∼10 min) umbilical cord occlusion (UCO) in fetal sheep at ∼0.88 gestation on fetal plasma cortisol concentrations and fetal behaviour [electrocortical (EcoG), electo-oculargram (EOG), nuchal muscle electromyography (EMG) and breathing activities] in the days following UCO. UCO caused a rapid onset of fetal hypoxaemia, hypercapnia, and acidosis; however, by 6 h, all blood parameters and cardiovascular status were normalized and not different from the control (Sham-UCO) cohort. Subsequently, the incidence of fetal breathing movements decreased compared to the control group, and abnormal behavioural patterns developed over the days following UCO and leading up to the onset of labour, which included increased high voltage and sub-low voltage ECoG and EOG activities, as well as decreased nuchal EMG activity. Fetuses subjected to UCO went into labour 7.9 ± 3.6 days post-UCO (139.5 ± 3.2 days of gestation) compared to the control group fetuses at 13.6 ± 3.3 days post-sham UCO (144 ± 2.2 days of gestation; P < 0.05), despite comparable increases in fetal plasma cortisol and a similar body weight at birth. Thus, a single transient episode of complete UCO late in gestation in fetal sheep can result in prolonged effects on fetal brain activity and premature labour, suggesting persisting effects on fetal cerebral metabolism.
UR - http://www.scopus.com/inward/record.url?scp=85107001765&partnerID=8YFLogxK
U2 - https://doi.org/10.1113/JP281266
DO - https://doi.org/10.1113/JP281266
M3 - Article
SN - 0022-3751
VL - 599
SP - 3221
EP - 3236
JO - The Journal of Physiology
JF - The Journal of Physiology
IS - 12
ER -